Antibodies to human tumor necrosis factor receptor-like 2

Abstract

The present invention relates to novel members of the Tumor Necrosis Factor family of receptors. The invention provides isolated nucleic acid molecules encoding a human TR2 receptor and two splice variants thereof. TR2 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of TR2 receptor activity. Also provided are diagnostic methods for detecting disease states related to the aberrant expression of TR2 receptors. Further provided are therapeutic methods for treating disease; states related to aberrant proliferation and differentiation of cells which express the TR2 receptors.

What is claimed is: 
     
       1. An isolated antibody which specifically binds to a polypeptide consisting of amino acids −38 to 245 of SEQ ID NO:26. 
     
     
       2. The isolated antibody of  claim 1 , wherein said antibody is a monoclonal antibody. 
     
     
       3. The isolated antibody of  claim 1 , wherein said antibody is a polyclonal antibody. 
     
     
       4. The isolated antibody of  claim 1 , wherein said antibody is a chimeric antibody. 
     
     
       5. The isolated antibody of  claim 1 , wherein said antibody is a humanized antibody. 
     
     
       6. The isolated antibody of  claim 1 , wherein said antibody is a single-chain Fv antibody. 
     
     
       7. The isolated antibody of  claim 1 , wherein said antibody is a Fab antibody. 
     
     
       8. A composition comprising the antibody of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
       9. An isolated antibody which binds to a polypeptide consisting of amino acids −38 to 162 of SEQ ID NO:26. 
     
     
       10. The isolated antibody of  claim 9  which binds to a polypeptide consisting of amino acids 1 to 162 of SEQ ID NO:26. 
     
     
       11. A composition comprising the antibody of  claim 9  and a pharmaceutically acceptable carrier. 
     
     
       12. The isolated antibody of  claim 1 , wherein said antibody is the product of an Fab expression library. 
     
     
       13. A method of producing the isolated antibody of  claim 1 , comprising:
 (a) immunizing an animal with a polypeptide comprising amino acids −38 to 245 of SEQ ID NO:26; and 
 (b) recovering an antibody, which specifically binds, said polypeptide. 
 
     
     
       14. A hybridoma which produces the monoclonal antibody of  claim 2 . 
     
     
       15. A method of producing a monoclonal antibody which comprises:
 (a) culturing the hybridoma of  claim 14  under appropriate conditions; and 
 (b) isolating monoclonal antibody therefrom. 
 
     
     
       16. An isolated antibody which specifically binds to a polypeptide consisting of amino acids −38 to 162 of SEQ ID NO:26. 
     
     
       17. The isolated antibody of  claim 16 , wherein said antibody is a monoclonal antibody. 
     
     
       18. The isolated antibody of  claim 16 , wherein said antibody is a polyclonal antibody. 
     
     
       19. The isolated antibody of  claim 16 , wherein said antibody is a chimeric antibody. 
     
     
       20. The isolated antibody of  claim 16 , wherein said antibody is a humanized antibody. 
     
     
       21. The isolated antibody of  claim 16 , wherein said antibody is a single-chain Fv antibody. 
     
     
       22. The isolated antibody of  claim 16 , wherein said antibody is an Fab antibody fragment. 
     
     
       23. The isolated antibody of  claim 16 , wherein said antibody is a product of an Fab expression library. 
     
     
       24. A composition comprising the antibody of  claim 16  and a pharmaceutically acceptable carrier. 
     
     
       25. A method of producing the isolated antibody of  claim 16 , comprising:
 (a) immunizing an animal with a polypeptide comprising amino acids −38 to 162 of SEQ ID NO:26; and 
 (b) recovering an antibody which specifically binds said polypeptide. 
 
     
     
       26. A hybridoma which produces the monoclonal antibody of  claim 17 . 
     
     
       27. A method of producing a monoclonal antibody which comprises:
 (a) culturing the hybridoma of  claim 26  under appropriate conditions; and 
 (b) isolating monoclonal antibody therefrom. 
 
     
     
       28. An isolated antibody which specifically binds to a polypeptide consisting of amino acids 1 to 162 of SEQ ID NO:26. 
     
     
       29. The isolated antibody of  claim 28 , wherein said antibody is a monoclonal antibody. 
     
     
       30. The isolated antibody of  claim 28 , wherein said antibody is a polyclonal antibody. 
     
     
       31. The isolated antibody of  claim 28 , wherein said antibody is a chimeric antibody. 
     
     
       32. The isolated antibody of  claim 28 , wherein said antibody is a humanized antibody. 
     
     
       33. The isolated antibody of  claim 28 , wherein said antibody is a single-chain Fv antibody. 
     
     
       34. The isolated antibody of  claim 28 , wherein said antibody is an Fab antibody fragment. 
     
     
       35. The isolated antibody of  claim 28 , wherein said antibody is the product of an Fab expression library. 
     
     
       36. A composition comprising the antibody of  claim 28  and a pharmaceutically acceptable carrier. 
     
     
       37. A method of producing the isolated antibody of  claim 28 , comprising:
 (a) immunizing an animal with a polypeptide comprising amino acids 1 to 162 of SEQ ID NO:26; and 
 (b) recovering an antibody, which specifically binds, said polypeptide. 
 
     
     
       38. A hybridoma which produces the monoclonal antibody of  claim 29 . 
     
     
       39. A method of producing a monoclonal antibody which comprises:
 (a) culturing the hybridoma of  claim 38  under appropriate conditions; and 
 (b) isolating monoclonal antibody therefrom. 
 
     
     
       40. An isolated antibody which binds to a polypeptide having the sequence of SEQ ID NO:26. 
     
     
       41. An isolated antibody that immunospecifically binds a tumor necrosis factor receptor, wherein said receptor comprises a polypeptide having the sequence of SEQ ID NO:26.